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利用猕猴桃增强黑色素瘤放射敏感性。

Harnessing the Power of Kiwifruit for Radiosensitization of Melanoma.

机构信息

HCA Healthcare/USF Morsani College of Medicine GME/St. Petersburg General Hospital, St. Petersburg, FL, U.S.A.

Department of Microbiology, Immunology & Pathology, Des Moines University College of Osteopathic Medicine, Des Moines, IA, U.S.A.

出版信息

Anticancer Res. 2021 Dec;41(12):5945-5951. doi: 10.21873/anticanres.15413.

Abstract

BACKGROUND

Melanoma is the deadliest variant of skin cancer and its incidence continues to increase. There are limited treatment options for advanced and metastatic cases of melanoma, despite advances in immunotherapy and chemotherapy. Melanoma is notorious as a radioresistant tumor. Previous studies found that phytochemicals, such as resveratrol and those found in green tea and blueberry, can sensitize various cancer cells, including melanoma, to radiotherapy. Our previous study also revealed that kiwifruit extract (KE) has antitumor activity to melanoma cells. This study was designed to expand upon our previous investigation and determine KE's potential as a radiosensitizer on CRL-11147 melanoma cancer cells and elucidate the possible mechanisms behind its potential.

MATERIALS AND METHODS

Proliferation and apoptosis of CRL-11147 melanoma cells under radiation therapy (RT) plus KE versus RT alone were investigated using Proliferative cell nuclear antigen (PCNA) staining, quick cell proliferation assay, clonogenic assay, and caspase-3 activity assay. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were then used to investigate the mechanisms behind the observed results.

RESULTS

The percentage of CRL-11147 colonies, PCNA staining intensity, and the optic density value of CRL-11147 cells decreased with RT/KE vs. RT alone. Relative caspase-3 activity was increased with RT/KE vs. RT alone. Increased expression of the anti-proliferative molecule p27 and pro-apoptotic molecule TRAILR1 correlated with the anti-tumor effect seen in the RT/KE group versus the RT alone group.

CONCLUSION

KE augments radiosensitivity of CRL-11147 by up-regulating both p27 and TRAILR1 to inhibit proliferation and increase apoptosis, respectively.

摘要

背景

黑色素瘤是皮肤癌中最致命的一种,其发病率持续上升。尽管免疫疗法和化疗有所进展,但对于晚期和转移性黑色素瘤病例,治疗选择有限。黑色素瘤是一种众所周知的放射抗拒肿瘤。先前的研究发现,植物化学物质,如白藜芦醇和绿茶及蓝莓中的物质,可以使包括黑色素瘤在内的各种癌细胞对放疗敏感。我们之前的研究还表明,猕猴桃提取物(KE)对黑色素瘤细胞具有抗肿瘤活性。本研究旨在扩展我们之前的研究,并确定 KE 作为 CRL-11147 黑色素瘤癌细胞放射增敏剂的潜力,并阐明其潜在机制。

材料和方法

通过增殖细胞核抗原(PCNA)染色、快速细胞增殖测定、集落形成测定和 caspase-3 活性测定,研究 CRL-11147 黑色素瘤细胞在放射治疗(RT)加 KE 与 RT 单独治疗下的增殖和凋亡情况。然后使用逆转录-聚合酶链反应(RT-PCR)和免疫组织化学(IHC)来研究观察结果背后的机制。

结果

与 RT 单独治疗相比,CRL-11147 集落的百分比、PCNA 染色强度和 CRL-11147 细胞的光密度值降低。与 RT 单独治疗相比,相对 caspase-3 活性增加。抗增殖分子 p27 和促凋亡分子 TRAILR1 的表达增加与 RT/KE 组与 RT 单独组相比的抗肿瘤作用相关。

结论

KE 通过上调 p27 和 TRAILR1 分别抑制增殖和增加凋亡,增强 CRL-11147 的放射敏感性。

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